Sensitive Determination of Felodipine in Human and Dog Plasma by Use of Liquid–Liquid Extraction and LC–ESI–MS–MS

Summary A sensitive and selective liquid chromatographic method coupled with electrospray ionization tandem mass spectrometry (LC–ESI–MS–MS) has been developed for quantification of felodipine in human and dog plasma. Compounds were separated on a 2.0 mm × 150 mm, 5.0 m particle, C₈ column with 1 m m ammonium acetate–acetonitrile, 20:80, pH 6.0, as mobile phase at a flow rate of 200 L min^–1. Nifedipine was used as internal standard. Plasma samples were extracted with diethyl ether, the centrifuged upper layer was evaporated, the residue was reconstituted with mobile phase, and the reconstituted samples were injected. The analytical column lasted for at least 1000 injections. By use of multiple reaction monitoring (MRM) mode in MS–MS felodipine and nifedipine were detected without severe interference from the human or dog plasma matrix. Felodipine produced a protonated precursor ion ([M + H]⁺) at m/z 384 and a corresponding product ion at m/z 338. And internal standard (nifedipine) produced a protonated precursor ion ([M + H]⁺) at m/z 347 and a corresponding product ion at m/z 315. Detection of felodipine in human and dog plasma was accurate and precise, with a limit of quantification of 0.05 ng mL^–1. The method has been successfully applied to preliminary pharmacokinetic study of felodipine in human and dog plasma.     

Efficient chemoselective deprotection of silyl ethers using catalytic 1-chloroethyl chloroformate in methanol

Fast and chemoselective desilylation of silyl-protected alcohols was achieved using a catalytic amount of 1-chloroethyl chloroformate in methanol. With a minimal amount of 1-chloroethyl chloroformate as the source for anhydrous HCl, extremely efficient cleavage of silyl ethers of primary and secondary alcohols was accomplished, and chemoselective deprotection of one silyl ether in the presence of another silyl or other acid-labile group was possible through controlling the amount of the chloroformate and reaction time.     

Enhanced reactivity and enantioselectivity in catalytic glyoxylate-ene reactions using chiral bis(oxazoline)–copper complex in an ionic liquid

An optimal hydrophobic ionic liquid was discovered as a solvent for highly enantioselective glyoxylate-ene reactions catalyzed by a chiral bis(oxazoline)–copper complex. The reactivity and stereoselectivity were highly dependent upon the property of the ionic liquids; reactions between olefins and ethyl glyoxylate in [Bmim]SbF₆ at ambient temperature provided remarkably enhanced reactivity and stereoselectivity, which greatly exceed those of the corresponding reactions in dichloromethane. Furthermore, the metal–ligand complex was readily recycled up to eight times while exhibiting no significant decrease in reaction efficiency.     

Development of Ultrasound-Assisted Extraction to Produce Skin-Whitening and Anti-Wrinkle Substances from Safflower Seed

In this study, ultrasound-assisted extraction (UAE) was applied to extract bioactive substances with skin-whitening, anti-wrinkle, and antioxidant effects from safflower seeds, and the extraction conditions were optimized by a central composite design. The independent variables, including extraction time (5.0~55.0 min), extraction temperature (26.0~94.0 °C), and ethanol concentration (0.0~100%), were optimized to increase tyrosinase activity inhibitory (TAI), collagenase activity inhibitory (CAI), and radical scavenging activity (RSA), which are indicators of skin-whitening, anti-wrinkle, and antioxidant effects. An extraction time of 26.4 min, extraction temperature of 52.1 °C, and ethanol concentration of 50.7% were found to be optimum conditions of UAE, under which TAI, CAI, and RSA were 53.3%, 91.5%, and 27.7%, respectively. The extract produced by UAE was analyzed by LC-MS/MS, and maleic acid and levulinic acid were identified as the main substances. Therefore, UAE is evaluated as an effective process to extract skin-whitening, anti-wrinkle, and antioxidant substances from safflower seeds at lower temperatures and shorter extraction times compared to the conventional extraction methods. Overall, safflower seeds extract can be used as a material for value-added cosmetics, including maleic acid and levulinic acid, which have bioactive functions.     

The Alleviating Effect of Lagerstroemia indica Flower Extract on Stretch Marks through Regulation of Mast Cells

Striae distensae (SD) or stretch marks are common linear scars of atrophic skin with disintegrating extracellular matrix (ECM) structures. Although fibroblasts contribute to the construction of ECM structure in SD, some studies have reported that mast cell degranulation causes the disruption of ECM in early SD lesions. Lagerstroemia indica flower (LIF) has traditionally been used in India as a diuretic. However, little is known about the effect and molecular action of Lagerstroemia indica flower extract (LIFE) on alleviating SD. This study evaluated the effects of LIFE on mast cell degranulation and the synthesis of ECM components in fibroblasts. LIFE inhibits the adhesion of rat basophilic leukemia (RBL) cells, RBL-2H3 on fibronectin (FN) and the expression of integrin, a receptor for FN, thereby reducing focal adhesion kinase (FAK) phosphorylation. In addition, LIFE attenuated the allergen-induced granules and cytokine interleukin 3 (IL-3) through the adhesion with FN. Moreover, the conditioned medium (CM) of activated mast cells decreases the synthesis of ECM components, and LIFE restores the abnormal expressions induced by activated mast cells. These results demonstrate that LIFE suppresses FN-induced mast cell activation and promotes the synthesis of ECM components in fibroblast, which indicates that LIFE may be a useful cosmetic agent for SD treatment.     

Molecular multivalent electrolytes: microstructure and screening lengths

We study small rod-like molecular electrolytes solutions with their corresponding atomic counterions. The asymptotic length scales (decay length and wavelength) of the structural correlations are analyzed using the formalism of the dressed interaction site theory (DIST). The correlation functions are determined using the reference interaction site model equation complemented with a mixed approach in which the hypernetted-chain closure is used for the repulsive interactions, and the mean spherical approximation is used for the attractive interactions. The results from this scheme are in good agreement with the Monte Carlo computer simulations reported here. The asymptotic properties of the correlation functions of this molecular system are compared against those corresponding to two related simple (atomic) electrolyte models. The main conclusion is that the molecular structure of the ions lowers by two orders of magnitude the concentration at which the transition from monotonic to oscillatory decay occurs.     

Reinterpretation of the molecular O2 chemisorbate in the initial oxidation of the si(111)7 x 7 surface

The initial oxygen adsorption on the Si(111)7 x 7 surface was investigated by high-resolution x-ray absorption spectroscopy. Below 220 K, a molecular adsorption species is identified by distinctive absorption resonances due to the 1 pi(g) molecular orbitals. The molecular species is metastabilized to have a lifetime of 15-35 min at 135 K only with the presence of atomic adsorbates of more than 0. 1 ML (monolayer). It is thus clearly evidenced that the very initial adsorption is dissociative even at 100 K and the molecular species is not a precursor state. The molecular adsorption structures with the coadsorbed oxygen atoms are suggested.     

Study of Internal Linear Inductively Coupled Plasma Source for Ultra Large-Scale Flat Panel Display Processing

An internal-type linear inductive antenna, which is referred to as “double comb-type antenna”, was used as a large-area inductively coupled plasma (ICP) source with a substrate area of 2,300 mm × 2,000 mm. The characteristics of the ICP source were investigated for potential applications to flat panel display (FPD) processing. The source showed higher power transfer efficiency at higher RF power and higher operating pressures. The power transfer efficiency was approximately 88.1% at 9 kW of RF power and a pressure of 20 mTorr Ar. This source showed increasing plasma density and improved plasma uniformity with increasing RF power at a given operating pressure. A plasma density >1.5 × 10¹¹/cm³ and a plasma uniformity of approximately 11% was obtained at 9 kW of RF power and 15 mTor Ar using this internal ICP source, which is applicable to FPD processing.